ATP and Liv-52 Ameliorate Linezolid-Induced Liver Injury via Modulation of NF-κB/NLRP3 Pathways

Objective: Linezolid (LZD), an oxazolidinone antibiotic widely used against Gram-positive infections, has been associated with mitochondrial dysfunction and hepatotoxicity, particularly during prolonged use. This study aimed to investigate the protective effects of adenosine triphosphate (ATP) and Liv-52 against LZD-induced liver injury, with a focus on oxidative stress, inflammation, and necroptosis pathways. Methods: Twenty-four male Wistar rats were randomly assigned to four groups: healthy control (HG), LZD-treated (LZDG), Liv-52 + LZD (LVLZ), and ATP + LZD (ATLZ). Liv-52 (50 mg/kg, orally) and ATP (5 mg/kg, intraperitoneally) were administered prior to LZD (125 mg/kg, orally) for 14 days. Results: Following LZD administration, malondialdehyde (MDA) levels markedly increased, indicating oxidative stress, while total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) activities significantly decreased. Histopathological examination revealed pronounced hepatocellular damage accompanied by increased NF-κB, NLRP3, RIPK3, and MLKL expression, indicating activation of inflammatory and necroptotic pathways. Treatment with ATP and Liv-52 significantly ameliorated these biochemical, histopathological, and molecular alterations. Conclusions: Treatment with ATP and Liv-52 significantly attenuated oxidative stress, improved histopathological alterations, and suppressed the expression of inflammatory and necroptotic markers. Notably, ATP exhibited a more pronounced protective effect compared to Liv-52. In conclusion, LZD induces hepatotoxicity through oxidative stress-mediated inflammatory and necroptotic mechanisms, while ATP and Liv-52 confer hepatoprotection, with ATP showing superior efficacy.